misoTar: A novel approach for predicting miRNA and isomiR targets

Understanding the interactions between microRNAs/isomiRs and mRNAs has long been a major challenge in RNA biology. Although numerous computational approaches have been developed to predict these interactions, most fail to account for isomiR mediated targeting. To address this limitation, we developed misoTar, a deep learning framework trained on more than 6.662 million positive and negative interaction pairs derived from 67 publicly available human samples across six independent studies. In five-fold cross-validation, misoTar achieved an average precision of 0.930 and a recall of 0.898. Evaluation on independent test datasets demonstrated consistently superior or comparable performance relative to existing tools, including TargetScan, Mimosa, DMISO, and TEC-miTarget. In addition, single-nucleotide mutation analyses of true positive interactions revealed the critical functional contributions of non-seed regions in microRNA/isomiR targeting. Overall, misoTar provides a robust and accurate framework for predicting microRNA/isomiR interactions while offering new biological insights into microRNA targeting mechanisms. The misoTar tool is publicly available at https://figshare.com/projects/misoTar/262723.